title: RNA editing of Kv1.1 channels may account for reduced ictogenic potential of 4-aminopyridine in chronic epileptic rats.
abstract: In rat brain slices, the Kv channel blocker 4-aminopyridine (4-AP) induces seizure-like events. This effect is absent in slices from chronic epileptic rats generated using the kainic acid model. The reason for this phenomenon remained elusive as an altered expression level of Kv channels was ruled out as a mechanism. We recently described that the Ile400Val RNA editing of Kv1.1 generates 4-AP-insensitive Kv1 channels (Kv1.1(I400V)). We therefore hypothesized that altered RNA editing levels account for the reduced ictogenic potency of 4-AP in chronic epileptic rats. We found fourfold increased RNA editing ratios in the entorhinal cortex of chronic epileptic animals compared to healthy control animals. Electrophysiologic recordings in Xenopus oocytes revealed that the observed increased Kv1.1(I400V) editing level can in fact lead to significant loss of 4-AP sensitivity. Our data suggest that altered Kv1.1(I400V) RNA editing contributes to the reduced ictogenic potential of 4-AP in chronic epileptic rats.
authors.affiliation: Institut für Physiologie und Pathophysiologie, Philipps-Universität Marburg, Marburg, Germany.
authors.forename: Anne Kathrin
authors.initials: AK
authors.lastname: Streit
authors.forename: Christian
authors.initials: C
authors.lastname: Derst
authors.forename: Sven
authors.initials: S
authors.lastname: Wegner
authors.forename: Uwe
authors.initials: U
authors.lastname: Heinemann
authors.forename: Robert K
authors.initials: RK
authors.lastname: Zahn
authors.forename: Niels
authors.initials: N
authors.lastname: Decher
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D003292:Convulsants / Q000494:pharmacology*; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000187:drug effects; D004827:Epilepsy / Q000139:chemically induced* / Q000235:genetics*; D006624:Hippocampus / Q000187:drug effects*; D051662:Kv1.1 Potassium Channel / Q000235:genetics*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D017393:RNA Editing / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D046509:Tissue Culture Techniques
chemical_list: D003292:Convulsants; C489293:Kcna1 protein, rat; D026902:Potassium Channel Blockers; D051662:Kv1.1 Potassium Channel; D015761:4-Aminopyridine